The effect of uremia on platelet contractile force, clot elastic modulus and bleeding time in hemodialysis patients.

INTRODUCTION: Uremic bleeding frequently occurs in dialysis patients. Although its mechanism is not well characterized, acquired platelet dysfunction has been implicated in its pathogenesis. Skin bleeding time has been used to characterize platelet dysfunction in this population. However, the bleeding time is prone to error. The goal of this study was to compare the bleeding time to the novel platelet function parameters platelet contractile force and clot elastic modulus as well as platelet aggregation studies in controls and patients receiving maintenance hemodialysis. MATERIALS AND METHODS: Forty-five subjects completed this study (25 controls, 20 dialysis). All subjects had the Ivy skin bleeding time procedure performed, as well as the collection of whole blood samples for the determination of platelet contractile force, clot elastic modulus, % von Willebrand Factor antigen, and platelet aggregation studies. Pearson's correlation determined the relationships between skin bleeding time and platelet function and clot structure parameters and markers of renal dysfunction. RESULTS: Bleeding time was significantly prolonged in the dialysis group relative to controls. The platelet function parameters were not significantly different between groups. There was a significant relationship between bleeding time and creatinine concentration, however, no relationship existed between bleeding time and platelet function parameters. CONCLUSIONS: Skin bleeding time poorly correlates with measurements of platelet function. There were no significant differences noted in platelet function between the groups despite the prolongations in bleeding time in the dialysis group. These data may suggest that the bleeding time reflects perturbations in platelet adhesion or secretion, and not aggregation. Further study is needed to characterize platelet function in dialysis patients.

Effect of high bicarbonate hemodialysis on ionized calcium and risk of metastatic calcification.

BACKGROUND: Disturbances in calcium and phosphate metabolism among chronic hemodialysis patients result in renal osteodystrophy and vascular calcification. Even though it is the ionized fraction of calcium that is metabolically active, this measurement is generally not available and decisions are made on the basis of total calcium. Formulae to predict ionized calcium concentrations are available. METHODS: The OPTI Critical Care Analyzer with E-Ca cuvettes was used on-site to measure acid-base parameters, electrolytes, and ionized calcium. Additional assays included total calcium, phosphate, and albumin. RESULTS: Using a dialysate with 1.25 or 1.5 mmol/l calcium and 40 mmol/l bicarbonate, we observed a statistically significant increase in pH and total CO2 concentrations in post-dialysis blood. Total and ionized calcium increased significantly only in the patients with central venous catheters but not in those with fistulas or grafts. All patients experienced a decrease in phosphate concentrations. CONCLUSIONS: The metabolic alkalosis induced by high bicarbonate dialysate was not associated with a decrease in ionized calcium or a change in the calculated concentration product ratio for hydroxyapatite formation in the immediate post-dialysis period. However, if a 40% phosphate rebound were to occur 2 h after termination of dialysis, the calculated risk of metastatic calcification would increase 2.8-fold compared to pre-dialysis conditions. Formulae to calculate ionized calcium are not useful in this population.

The effect of hemodialysis on electrolytes and acid-base parameters.

BACKGROUND: Hemodialysis patients are treated with bicarbonate dialysate to correct the metabolic acidosis, which results from the metabolism of dietary and endogenous protein. The concentration of plasma tCO(2) is used to gauge the success of therapy. Reported low values in pre-dialysis blood suggest incomplete correction of acidosis in a substantial percent of the dialysis population. However, questions have been raised about the reliability of tCO(2) determination in dialysis patients. METHODS: Pre- and post-dialysis blood specimens were obtained from chronic hemodialysis patients and analyzed on-site using an OPTI Critical Care Analyzer. Results were compared with reports obtained monthly from the reference laboratory to which the samples were routinely shipped for analysis. In addition, OPTI analyzer whole blood electrolytes were compared with plasma electrolytes determined in a local laboratory. RESULTS: Mid-week testing of patients dialyzed against a 40-mmol/l bicarbonate dialysate found that most patients had normal acid-base status pre-dialysis and frank metabolic alkalosis by the end of dialysis. Whole blood tCO(2) values determined on the OPTI CCA were 2.4 mmol/l greater than heparin plasma tCO(2) assayed on the Vitros chemistry analyzer. Small differences were also observed for K(+) and Cl(-). CONCLUSIONS: Based on our on-site determination of acid-base and electrolyte concentrations, metabolic acidosis appears to be fully correctable in well-dialyzed renal failure patients. Metabolic alkalosis is apparent in the post-dialysis period.

Loss of carbon dioxide from serum samples exposed to air. Effect on blood gas parameters and strong ions.

BACKGROUND: The acid-base status of patients is frequently inferred from the concentration of total carbon dioxide in a venous blood sample. Prior studies of hemodialysis patients have reported lower values for tCO(2) when blood is shipped to a distant central laboratory compared to samples assayed at a local laboratory. Loss of tCO(2) from the sample after exposure of the blood to room air was postulated as the predominant factor. METHODS: Serum samples were assayed on-site before and at varying intervals after removing the tube stopper on an AVL OPTI Critical care Analyzer using E-Cl cuvettes. RESULTS: A rapid and progressive decline in pCO(2) and increase in pH was documented over a 2 h period. However, the change in tCO(2) during this time period was small and not significant. There were no changes in the concentrations of strong ions. CONCLUSIONS: The discrepancy in tCO(2) reported previously cannot be attributed solely to rapid loss of CO(2) unless assay conditions greatly enhance the rate of loss compared to the experimental conditions used in this study.

Correlation studies of plasma paraoxonase activity and uric acid concentration with AAPH-Induced erythrocyte hemolysis in hemodialysis patients.

Uric acid possesses antioxidant properties and is an important determinant of total plasma antioxidant capacity. Uric acid concentrations tend to be elevated in patients with renal failure requiring maintenance hemodialysis but are abruptly reduced by the dialysis procedure itself. Paraoxonase (PON1), an enzyme which circulates in association with high density lipoprotein (HDL), confers protection against free radicals by limiting the oxidation of phospholipids. The relationship between pre- and postdialysis uric acid concentration, PON1 activity, and high density lipoprotein cholesterol (HDL-C) level and the resistance of erythrocytes from hemodialysis patients to hemolysis induced by the free radical generator 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) was studied. Red cells were washed free of plasma prior to the assay, and no plasma was added to the hemolysis assay tubes. Postdialysis erythrocytes were found to be more susceptible to hemolysis compared to blood samples obtained at the initiation of the session (784 +/- 713 vs. 256 +/- 256 micro mol/L hemoglobin released after 60 min incubation and 1530 +/- 696 vs. 1354 +/- 757 micro mol/L at 90 min). Hemolysis correlated negatively with the concentration of uric acid and positively with PON1 arylesterase activity but not with HDL-C level in the corresponding plasma samples. There was a strong negative correlation between uric acid and PON1 in predialysis blood samples (r2 = 0.4, P < 0.001). The conclusion is that the reciprocal relationship between uric acid and PON1 may reflect a mechanism that protects erythrocytes from subsequent oxidative stress.